Studies were directed toward determining the steps involved in the differentiation of B cells into immunoglobulin synthesizing and secreting plasma cells. Special emphasis was laid on developing new techniques to study the role of helper T cells, macrophages, and suppressor cells in these immune regulatory processes and to define defects in these immunoregulatory cell interactions in patients with immune dysfunctions. Leukemias of prosuppressor, suppressor effector and helper T cells have been identified. Excessive numbers of suppressor T cells have been demonstrated in association with agammaglobulinemia selective IgA deficiency, suppressor leukemias, infectious mononucleosis, and post transplantation immunodeficiency states, antigen nonspecific suppressor factors that inhibit B cell immunoglobulin synthesis have been identified in the supernatants of cultured human T cell lines and T-T cell hybridomas. Recombinant DNA technology has been applied to study the arrangement and rearrangement of immunoglobulin genes in lymphocytic leukemias and in lymphocyte cell lines. In these studies it was shown that human B-cells rearrange the genes in the expressed allele and may retain, rearrange, or delete the non-expressed allele. Unexpectedly the kappa gene was deleted in lamda expressing B cells.